Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles
Abstract Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12243 |
| _version_ | 1811339544351473664 |
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| author | Xiao Xiong Xiurong Ke Lu Wang Yusheng Lin Shuhong Wang Zhimeng Yao Kai Li Yichen Luo Fan Liu Yunlong Pan Sai‐Ching J. Yeung Wijnand Helfrich Hao Zhang |
| author_facet | Xiao Xiong Xiurong Ke Lu Wang Yusheng Lin Shuhong Wang Zhimeng Yao Kai Li Yichen Luo Fan Liu Yunlong Pan Sai‐Ching J. Yeung Wijnand Helfrich Hao Zhang |
| author_sort | Xiao Xiong |
| collection | DOAJ |
| description | Abstract Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription‐induced chimeric RNA, designated A‐PaschiRNA, as a possible source of clinically relevant and targetable neoantigens. A‐PaschiRNA encodes a recently discovered cancer‐specific chimeric protein that comprises full‐length astrotactin‐2 (ASTN2) C‐terminally fused in‐frame to the antisense sequence of the 18th intron of pregnancy‐associated plasma protein‐A (PAPPA). We used extracellular vesicles (EVs) from A‐PaschiRNA‐transfected dendritic cells (DCs) to produce the cell‐free anticancer vaccine DEXA‐P. Treatment of immunocompetent cancer‐bearing mice with DEXA‐P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer‐specific transcription‐induced chimeric RNAs can be exploited to produce a cell‐free cancer vaccine that induces potent CD8+ T cell‐mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation‐based antigens. Moreover, this cell‐free anticancer vaccine approach may offer several practical advantages over cell‐based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life. |
| first_indexed | 2024-04-13T18:28:16Z |
| format | Article |
| id | doaj.art-243a65420eaa4f3a8de40b1aa3f2e802 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-04-13T18:28:16Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-243a65420eaa4f3a8de40b1aa3f2e8022022-12-22T02:35:10ZengWileyJournal of Extracellular Vesicles2001-30782022-08-01118n/an/a10.1002/jev2.12243Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesiclesXiao Xiong0Xiurong Ke1Lu Wang2Yusheng Lin3Shuhong Wang4Zhimeng Yao5Kai Li6Yichen Luo7Fan Liu8Yunlong Pan9Sai‐Ching J. Yeung10Wijnand Helfrich11Hao Zhang12Institute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaDepartment of Surgery Laboratory for Translational Surgical Oncology University of Groningen University Medical Center Groningen Groningen The NetherlandsInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaInstitute of Precision Cancer Medicine and Pathology, and Department of Pathology School of Medicine and Department of General Surgery The First Affiliated Hospital of Jinan University Jinan University Guangzhou Guangdong ChinaDepartment of General Surgery The First Affiliated Hospital of Jinan University, and Institute of Precision Cancer Medicine and Pathology School of Medicine Jinan University Guangzhou Guangdong ChinaDepartment of Emergency Medicine University of Texas MD Anderson Cancer Center Houston Texas USADepartment of Surgery Laboratory for Translational Surgical Oncology University of Groningen University Medical Center Groningen Groningen The NetherlandsDepartment of General Surgery The First Affiliated Hospital of Jinan University, and Institute of Precision Cancer Medicine and Pathology School of Medicine Jinan University Guangzhou Guangdong ChinaAbstract Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription‐induced chimeric RNA, designated A‐PaschiRNA, as a possible source of clinically relevant and targetable neoantigens. A‐PaschiRNA encodes a recently discovered cancer‐specific chimeric protein that comprises full‐length astrotactin‐2 (ASTN2) C‐terminally fused in‐frame to the antisense sequence of the 18th intron of pregnancy‐associated plasma protein‐A (PAPPA). We used extracellular vesicles (EVs) from A‐PaschiRNA‐transfected dendritic cells (DCs) to produce the cell‐free anticancer vaccine DEXA‐P. Treatment of immunocompetent cancer‐bearing mice with DEXA‐P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer‐specific transcription‐induced chimeric RNAs can be exploited to produce a cell‐free cancer vaccine that induces potent CD8+ T cell‐mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation‐based antigens. Moreover, this cell‐free anticancer vaccine approach may offer several practical advantages over cell‐based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life.https://doi.org/10.1002/jev2.12243EV‐based cancer vaccinemutation‐independent neoantigentranscription‐induced chimeric RNA |
| spellingShingle | Xiao Xiong Xiurong Ke Lu Wang Yusheng Lin Shuhong Wang Zhimeng Yao Kai Li Yichen Luo Fan Liu Yunlong Pan Sai‐Ching J. Yeung Wijnand Helfrich Hao Zhang Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles Journal of Extracellular Vesicles EV‐based cancer vaccine mutation‐independent neoantigen transcription‐induced chimeric RNA |
| title | Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles |
| title_full | Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles |
| title_fullStr | Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles |
| title_full_unstemmed | Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles |
| title_short | Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles |
| title_sort | neoantigen based cancer vaccination using chimeric rna loaded dendritic cell derived extracellular vesicles |
| topic | EV‐based cancer vaccine mutation‐independent neoantigen transcription‐induced chimeric RNA |
| url | https://doi.org/10.1002/jev2.12243 |
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